rs3124955

chr9-134882699-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004108.3(FCN2):c.214+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,207,266 control chromosomes in the GnomAD database, including 75,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8131 hom., cov: 32)
  • Exomes 𝑓: 0.36 (67735 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.214+60T>C		intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.101-603T>C		intron_variant
FCN2	XM_006717015.5	c.68-603T>C		intron_variant
FCN2	XM_011518392.4	c.181+60T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.214+60T>C		intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.101-603T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48825 AN: 151768 Hom.: 8123 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.357 AC: 377017 AN: 1055380 Hom.: 67735 AF XY: 0.360 AC XY: 194455 AN XY: 540280

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.322 AC: 48837 AN: 151886 Hom.: 8131 Cov.: 32 AF XY: 0.322 AC XY: 23913 AN XY: 74226

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.359

Alfa AF: 0.323 Hom.: 1480

Bravo AF: 0.315

Asia WGS AF: 0.419 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.16
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3124955; hg19: chr9-137774545; COSMIC: COSV52477137;